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Differential diagnosis of dementias using in vivo MRI and data-driven disease progression modelling: a case study in Alzheimer's disease and dementia with Lewy bodies

Castro Leal, G.; Konuri, A.; Young, A. L.; Zebarjadi, N.; Habich, A.; Castellanos-Perilla, N.; Camila Gonzalez, M.; Taylor, J.-P.; Firbank, M.; Lewis, S. J. G.; Alcolea, D.; Bejanin, A.; Segers, K.; Isik, A. T.; Samanci, B.; Chafer-Pericas, C.; Lambert, C.; Landin-Romero, R.; Bhome, R.; Dobreva, I.; Weil, R. S.; Walker, Z.; Aarsland, D.; Westman, E.; Ferreira, D.; Matar, E.; Oxtoby, N. P.

2025-10-08 neurology
10.1101/2025.10.03.25337171 medRxiv
Show abstract

Alzheimers disease (AD) and Dementia with Lewy bodies (DLB) are neurodegenerative diseases often sharing clinical symptoms, causing frequent misdiagnoses. Using data from multiple cohorts we improve and apply the SuStaIn algorithm on regional brain volumes from magnetic resonance imaging (MRI), then assess biomarker/phenotype/histopathology associations among the discovered atrophy subtypes. The three data-driven subtypes of brain atrophy show divergent clinical/biomarker/histopathological profiles that could support differential diagnosis. Both clinical syndrome and post-mortem diagnosis aligned imperfectly but plausibly with subtype: Limbic (more AD), Cortical (more DLB). The Limbic subtype showed lower cerebrospinal fluid (CSF) amyloid-{beta}, higher CSF phosphorylated tau, worse memory, and fewer hallucinations than the Cortical subtype. Our novel data-driven transdiagnostic approach shows promise for supporting in vivo differential diagnosis using only MRI.

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